ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

ObjectiveTo investigate the efficacy of selective internal radiation therapy （SIRT） in patients with unresectable hepatocellular carcinoma， and to provide a reference for the selection of clinical treatment regimens. MethodsA retrospective analysis was performed for the clinical data of 73 patients with unresectable hepatocellular carcinoma who received yttrium-90 microsphere SIRT in Eastern Hepatobiliary Surgery Hospital from May 1， 2023 to September 1， 2024. According to tumor characteristics， physical status， liver reserve function， laboratory tests， and SIRT treatment strategy， the patients were divided into radiation segmentectomy group with 9 patients， conversion therapy group with 47 patients， and palliative treatment group with 17 patients. Based on the results of postoperative follow-up， modified Response Evaluation Criteria in Solid Tumors were used to assess radiographic images. A one-way analysis of variance was used for comparison of normally distributed continuous data between three groups， and the chi-square test was used for comparison of categorical data between three groups； the Logistic regression model was used to perform the multivariate analysis. ResultsThere was a significant difference in postoperative outcome between the radiation segmentectomy group， the conversion therapy group， and the palliative treatment group （χ²=30.060， P<0.001）. The disease control rate was 100.0% （9/9） in the radiation segmentectomy group， 83.0% （39/47） in the conversion therapy group， and 29.4% （5/17） in the palliative treatment group， with a significant difference between the three groups （χ²=19.575， P<0.001）， and there was also a significant difference in objective response rate between the three groups （χ²=17.749， P<0.001）. The multivariate Logistic regression analysis showed that the number of tumors （odds ratio ［OR］=0.085， 95% confidence interval ［CI］： 0.008 — 0.906， P=0.041） and combined targeted immunotherapy （OR=18.808， 95%CI： 1.704 — 207.616， P=0.017） were independent influencing factors for achieving complete response. ConclusionThe number of tumors is an independent influencing factor for the efficacy of SIRT and is an important basis for selecting different treatment goals. SIRT combined with targeted immunotherapy may achieve better efficacy.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

OBJECTIVE To systematically compare mature experiences of comprehensive drug value assessment in typical countries/regions and to provide decision-making references for China to establish a scientific and standardized comprehensive drug value assessment system for medical-insured drugs. METHODS The literature analysis was used to systematically review drug value assessment frameworks in 11 representative countries/regions， namely the UK， Canada， Italy， Australia， Germany， France， South Korea， Japan， the United States， as well as Taiwan （China） and Hong Kong （China）. Comparisons were made across three dimensions： assessment entities， value dimension， and application of results. RESULTS &CONCLUSIONS In most countries/regions， independent technical assessment institutions have been established as part of the drug value evaluation system， with the involvement of multiple stakeholders （e.g.， the UK， Canada）. The mainstream drug value assessment frameworks have generally transcended the traditional core dimensions of safety， efficacy， and cost-effectiveness， exhibiting two major trends： the continuous expansion of assessment dimensions and stricter evidence requirements. Assessment outcomes are closely integrated with payment policies， ranging from providing technical advice for decision-making （e.g.， Italy， France） to directly determining reimbursement eligibility （e.g.， the UK， Germany）. The following recommendations are proposed for China： first， establish an evaluation mechanism featuring multi-stakeholder participation and separation of evaluation from decision-making. Second， develop a comprehensive evaluation framework integrating clinical， economic， patient， and societal value， emphasizing quantitative indicator exploration and real-world evidence application. Third， promote direct linkage between value-based tiering outcomes and medical insurance reimbursement decisions or access negotiations to balance patient benefits， fund sustainability， and industrial innovation.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

Objective:To investigate the characteristics of the population of skeletal fluorosis patients in drinking-tea-borne endemic fluorosis (referred to as drinking-tea-borne fluorosis) areas in Inner Mongolia Autonomous Region (referred to as Inner Mongolia) and the influencing factors of treatment willingness, and to provide a basis for improving the prevention and control measures of drinking-tea-borne fluorosis and the treatment plan of skeletal fluorosis.Methods:From August to October 2022, a face-to-face questionnaire survey was conducted in key areas of drinking-tea-borne fluorosis in Inner Mongolia (administrative villages with an average daily intake of tea fluoride > 3.5 mg and skeletal fluorosis patients identified by the general survey of drinking-tea-borne fluorosis in Inner Mongolia in 2019), and to investigate the demographic, severity, and treatment status of patients with skeletal fluorosis, analyze the demographic characteristics of patients with skeletal fluorosis and the influencing factors of treatment willingness.Results:A total of 734 patients with skeletal fluorosis were investigated, including 543 mild cases, 125 moderate cases and 66 severe cases. The gender ratio of patients with skeletal fluorosis was 0.71 ∶ 1.00 (305/429), the age was concentrated in > 50 - 70 years old (70.57%, 518/734), the proportion of Mongolians was 94.28% (692/734), the proportion of herders was 97.68% (717/734), the educational level was mainly primary school (54.63%, 401/734), and the proportion of poor households and immigrants who had moved to their current residence was 7.08% (52/734) and 8.04% (59/734), respectively. The distribution of the severity of skeletal fluorosis in patients of different ages, genders, and educational levels was compared, and the differences were statistically significant ( P < 0.05). Fifty-three point two seven percent (391/734) of the patients had a willingness to undergo non-pharmacological treatment, of which 69.82% (273/391) had already started non-pharmacological treatment, with a treatment effectiveness rate of 73.99% (202/273). Sixty-five point two six percent (479/734) of the patients had a willingness to receive medication treatment, of which 7.31% (35/479) had already started medication treatment, with a treatment effectiveness rate of 54.29% (19/35). Zero point two seven percent (2/734) of the patients expressed a willingness to undergo surgical treatment, while no patients underwent surgical treatment. Multivariate logistic regression analysis showed that the age, ethnicity, occupation, educational level, poverty status, immigrants status, and the severity of skeletal fluorosis were all influencing factors of non-pharmacological treatment willingness ( P < 0.05). Occupation, educational level, poverty status, immigrants status, and the severity of skeletal fluorosis were all influencing factors of medication treatment willingness ( P < 0.05). Conclusions:Patients with skeletal fluorosis caused by tea drinking in Inner Mongolia are mainly from Mongolian ethnic groups, herders, middle-aged and elderly people, and those with a lower educational levels. The willingness of patients to receive treatment is influenced by various factors, and corresponding intervention measures can be formulated and taken based on these influencing factors to effectively improve the disease prevention awareness and treatment willingness of patients and the public.

Objective:To study the relationship between urinary arsenic methylation metabolism patterns and skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water.Methods:Using a cross-sectional study method, a survey on endemic arsenic poisoning was conducted among permanent residents of drinking water endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region in 2004 (before water improvement). In 2017 (after water improvement), 71 arsenic exposed individuals were followed up as survey subjects. According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the clinical grading of skin injuries (skin keratinization, pigmentation abnormalities) in the survey subjects was evaluated. Urine samples were collected for detection of arsenic methylation metabolite levels by high-performance liquid chromatography inductively coupled plasma mass spectrometry and calibrated with urinary creatinine. The changes and amplitudes of urinary arsenic methylation indicators before and after water improvement were calculated and analyzed according to the outcome of skin keratinization and pigmentation abnormalities which were divided into reduced, unchanged, and added groups.Results:(1) The changes in urinary total arsenic (TAs), inorganic arsenic (iAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) levels in different outcome groups of skin keratinization were compared, and the differences were statistically significant ( H = 9.08, 8.77, 9.28, 8.57, P < 0.05). The changes in urinary TAs, iAs, MMA, DMA levels, iAs percentage (iAs%), DMA percentage (DMA%), and primary methylation index (PMI) in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 8.04, 10.67, 8.29, 9.14, 6.30, 9.10, 7.20, P < 0.05). (2) The comparison of amplitudes in urinary TAs, iAs, MMA, and DMA levels in different outcome groups of skin keratinization showed statistically significant differences ( H = 6.92, 7.34, 6.66, 6.16, P < 0.05). The amplitudes in urinary iAs level, iAs%, DMA%, and PMI in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 7.94, 7.61, 9.95, 7.22, P < 0.05). Conclusion:The changes pattern of urinary TAs, iAs, MMA, DMA, iAs%, DMA%, and PMI in population exposed to arsenic through drinking water is related to the transformation of skin keratinization and pigmentation abnormalities.

Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.

Gallbladder cancer is a highly aggressive malignancy of the biliary system, often diagnosed at the advanced stage due to its insidious early symptoms, leading to poor overall progno-sis. In recent years, the rapid advancement of artificial intelligence (AI) technologies and their inte-gration into medicine have opened new avenues for the early diagnosis and precision treatment of gallbladder cancer. Currently, AI incorporating deep learning algorithm has significantly improved diagnostic sensitivity and specificity in ultrasound, computed tomography, and pathological analysis. However, clinical translation of AI models remains limited by challenges such as insufficient annota-ted data and limited model interpretability. Future research should focus on establishing multi-center data-sharing mechanisms, developing interpretability tools, and optimizing multimodal data integration strategies, thereby promoting the transformation of AI technologies from an auxiliary diagnostic tool to a core component of clinical decision-making.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.